Associate Professor of Medicine and of Physiology
Associate Chief of Staff for Research and Development (VA)
Dr. Robey received his B.S. with Honors in Chemical Biology from Rhodes College in 1981 and his M.D. from the University of Arkansas in 1985. After completing his internship and residency in Internal Medicine at the University of Arkansas in 1988, he received a National Research Service Award to train in the Laboratory of Kidney and Electrolyte Metabolism at NIH (NHLBI). In 1991, he moved to the Vanderbilt University School of Medicine, where he completed both clinical training in Nephrology and a postdoctoral research fellowship in Physiology and Biophysics. In 1996, he accepted a faculty position at the University of Illinois at Chicago College of Medicine, where he remained until accepting his present positions in 2005. He is an Established Investigator of the American Heart Association, a Fellow of the American Society of Nephrology, and plays an active role in activities of the American Physiological Society.
Dr. Robey’s principal scientific interests involve the regulation and function of mammalian hexokinases which play a central role in normal cellular glucose uptake and utilization. His laboratory employs a wide array of molecular, biochemical, and cell physiologic approaches to the study of hexokinase regulation and function. The lab is presently exploring the teleologic relationship between metabolism and cell survival, focusing specifically upon a novel role played by mitochondria-bound hexokinases in mediating the anti-apoptotic effects of growth factors. Originally recognized as a potential adaptive function in 'normal' cells, the lab is now also exploring its putative maladaptive counterpart in tumor cells, where increases in hexokinase activity and mitochondrial interaction are thought to contribute to both the classical glycolysis-dependent phenotype of cancer cells and their intrinsic resistance to cell death. As such, these studies have profound physiologic, pathophysiologic, and therapeutic implications. It is anticipated that a better understanding of hexokinase regulation and associated adaptive and maladaptive functions will ultimately lead to the identification of specific therapeutic targets for altering cellular susceptibility to death. In principle, this could ultimately lead to specific strategies for minimizing normal tissue injury or, conversely, for increasing the efficacy of cytotoxic cancer therapies.
Robey RB, Ruiz O, Santos AVP, Ma J, Kear F, Wang L-J, Li C-J, Bernardo AA, and Arruda JAL. pH-dependent fluorescence of a heterologously expressed Aequorea green fluorescent protein mutant: In situ spectral characteristics and applicability to intracellular pH estimation. Biochemistry 37:9894-901, 1998.
Robey RB, Ma J, and Santos AVP. Regulation of mesangial cell hexokinase activity by PKC and the classic MAPK pathway. American Journal of Physiology: Renal Physiology 277:F742-9, 1999.
Robey RB, Raval BJ, Ma J, and Santos AVP. Thrombin is a novel regulator of hexokinase activity in mesangial cells. Kidney Int 57:2308-18, 2000.
Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, and Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes and Development 15:1406-18, 2001.
Bryson JM, Coy PE, Gottlob K, Hay N, and Robey RB. Increased hexokinase activity, of either ectopic or endogenous origin, protects renal epithelial cells against acute oxidant-induced cell death. Journal of Biological Chemistry 277:11392-400, 2002.
Robey RB, Ma J, Santos AVP, Noboa OA, Coy PE, and Bryson JM. Regulation of mesangial cell hexokinase activity and expression by heparin-binding epidermal growth factor-like growth factor: Epidermal growth factors and phorbol esters increase glucose metabolism via a common mechanism involving classic mitogen-activated protein kinase pathway activation and induction of hexokinase II expression. Journal of Biological Chemistry 277:14370-8, 2002.
Coy PE, Taneja N, Lee I, Hecquet C, Bryson JM, and Robey RB. LPA is a novel lipid regulator of mesangial cell hexokinase activity and HKII isoform expression. American Journal of Physiology: Renal Physiology 283:F271-9, 2002.
Majewski N, Nogueira V, Robey RB, and Hay N. Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Molecular and Cellular Biology 24:730-40, 2004.
Taneja N, Coy PE, Lee I, Bryson JM, and Robey RB. Proinflammatory interleukin-1 cytokines increase mesangial cell hexokinase activity and hexokinase II isoform expression. American Journal of Physiology: Cell Physiology 287:C548-57, 2004.
Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen J, Gottlob K, Chandel NS, Thompson CB, Robey RB, and Hay N. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Molecular Cell 16:819-30, 2004.
Robey RB and Hay N. Mitochondrial hexokinases: Guardians of the mitochondria. Cell Cycle 4:654-8, 2005.
Robey RB and Hay N. Akt, hexokinase, mTOR: Targeting cellular energy metabolism for cancer therapy. Drug Discovery Today — Disease Mechanisms 2:239-46, 2005 (Erratum: Drug Discovery Today — Disease Mechanisms 2:389, 2005).
Robey RB and Hay N. Mitochondrial hexokinases, novel mediators of the anti-apoptotic effects of growth factors and Akt. Oncogene 25:4683-96, 2006.
04/26/07